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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:CASK-GLIPR1L1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CASK-GLIPR1L1
FusionPDB ID: 13195
FusionGDB2.0 ID: 13195
HgeneTgene
Gene symbol

CASK

GLIPR1L1

Gene ID

8573

256710

Gene namecalcium/calmodulin dependent serine protein kinaseGLIPR1 like 1
SynonymsCAGH39|CAMGUK|CMG|FGS4|LIN2|MICPCH|MRXSNA|TNRC8|hCASKALKN2972|PRO7434
Cytomap

Xp11.4

12q21.2

Type of geneprotein-codingprotein-coding
Descriptionperipheral plasma membrane protein CASKcalcium/calmodulin-dependent serin protein kinasecalcium/calmodulin-dependent serine protein kinase (MAGUK family)calcium/calmodulin-dependent serine protein kinase membrane-associated guanylate kinaseprotein linGLIPR1-like protein 1GLI pathogenesis related 1 like 1
Modification date2020032720200313
UniProtAcc

Q8WXE0

Main function of 5'-partner protein:

Q6UWM5

Main function of 5'-partner protein: FUNCTION: Plays a role in the binding between sperm and oocytes. Component of epididymosomes, one type of membranous microvesicules which mediate the transfer of lipids and proteins to spermatozoa plasma membrane during epididymal maturation. Also component of the CD9-positive microvesicules found in the cauda region. {ECO:0000250|UniProtKB:Q32LB5, ECO:0000250|UniProtKB:Q9DAG6}.
Ensembl transtripts involved in fusion geneENST idsENST00000318588, ENST00000361962, 
ENST00000378154, ENST00000378158, 
ENST00000378163, ENST00000378166, 
ENST00000421587, ENST00000442742, 
ENST00000472704, 
ENST00000548623, 
ENST00000312442, ENST00000378695, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 12 X 5=7806 X 5 X 4=120
# samples 147
** MAII scorelog2(14/780*10)=-2.47804729680464
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/120*10)=-0.777607578663552
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CASK [Title/Abstract] AND GLIPR1L1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CASK [Title/Abstract] AND GLIPR1L1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CASK(41782183)-GLIPR1L1(75737473), # samples:3
Anticipated loss of major functional domain due to fusion event.CASK-GLIPR1L1 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
CASK-GLIPR1L1 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneCASK

GO:0010839

negative regulation of keratinocyte proliferation

18664494



check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chrX:41782183/chr12:75737473)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.
FGviewer

check buttonRetention analysis results of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features, are available here.

check buttonFusion gene breakpoints across CASK (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across GLIPR1L1 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000421587CASKchrX41782183-ENST00000378695GLIPR1L1chr1275737473+70483107637176
ENST00000421587CASKchrX41782183-ENST00000312442GLIPR1L1chr1275737473+99583107610167
ENST00000318588CASKchrX41782183-ENST00000378695GLIPR1L1chr1275737473+72610521659212
ENST00000318588CASKchrX41782183-ENST00000312442GLIPR1L1chr1275737473+101710521632203
ENST00000361962CASKchrX41782183-ENST00000378695GLIPR1L1chr1275737473+72610521659212
ENST00000361962CASKchrX41782183-ENST00000312442GLIPR1L1chr1275737473+101710521632203
ENST00000378163CASKchrX41782183-ENST00000378695GLIPR1L1chr1275737473+11555342971088263
ENST00000378163CASKchrX41782183-ENST00000312442GLIPR1L1chr1275737473+14465342971061254
ENST00000378158CASKchrX41782183-ENST00000378695GLIPR1L1chr1275737473+1031410173964263
ENST00000378158CASKchrX41782183-ENST00000312442GLIPR1L1chr1275737473+1322410173937254
ENST00000378166CASKchrX41782183-ENST00000378695GLIPR1L1chr1275737473+707862640212
ENST00000378166CASKchrX41782183-ENST00000312442GLIPR1L1chr1275737473+998862613203
ENST00000442742CASKchrX41782183-ENST00000378695GLIPR1L1chr1275737473+69978102632176
ENST00000442742CASKchrX41782183-ENST00000312442GLIPR1L1chr1275737473+99078102605167
ENST00000378154CASKchrX41782183-ENST00000378695GLIPR1L1chr1275737473+11555342971088263
ENST00000378154CASKchrX41782183-ENST00000312442GLIPR1L1chr1275737473+14465342971061254

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000421587ENST00000378695CASKchrX41782183-GLIPR1L1chr1275737473+0.011781290.98821867
ENST00000421587ENST00000312442CASKchrX41782183-GLIPR1L1chr1275737473+0.012170870.9878291
ENST00000318588ENST00000378695CASKchrX41782183-GLIPR1L1chr1275737473+0.0121552750.98784465
ENST00000318588ENST00000312442CASKchrX41782183-GLIPR1L1chr1275737473+0.0097485890.9902514
ENST00000361962ENST00000378695CASKchrX41782183-GLIPR1L1chr1275737473+0.0121552750.98784465
ENST00000361962ENST00000312442CASKchrX41782183-GLIPR1L1chr1275737473+0.0097485890.9902514
ENST00000378163ENST00000378695CASKchrX41782183-GLIPR1L1chr1275737473+0.0328748560.9671252
ENST00000378163ENST00000312442CASKchrX41782183-GLIPR1L1chr1275737473+0.0226110130.977389
ENST00000378158ENST00000378695CASKchrX41782183-GLIPR1L1chr1275737473+0.0322941540.9677058
ENST00000378158ENST00000312442CASKchrX41782183-GLIPR1L1chr1275737473+0.0159882770.98401165
ENST00000378166ENST00000378695CASKchrX41782183-GLIPR1L1chr1275737473+0.0127687890.9872312
ENST00000378166ENST00000312442CASKchrX41782183-GLIPR1L1chr1275737473+0.0122494070.9877506
ENST00000442742ENST00000378695CASKchrX41782183-GLIPR1L1chr1275737473+0.0119609740.98803896
ENST00000442742ENST00000312442CASKchrX41782183-GLIPR1L1chr1275737473+0.011561560.9884384
ENST00000378154ENST00000378695CASKchrX41782183-GLIPR1L1chr1275737473+0.0328748560.9671252
ENST00000378154ENST00000312442CASKchrX41782183-GLIPR1L1chr1275737473+0.0226110130.977389

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for CASK-GLIPR1L1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CASKchrX41782183GLIPR1L1chr127573747310528VRGCVRAVRGDRKIWDKGLAKMAKAW
CASKchrX41782183GLIPR1L1chr127573747341079VRGCVRAVRGDRKIWDKGLAKMAKAW
CASKchrX41782183GLIPR1L1chr127573747353479VRGCVRAVRGDRKIWDKGLAKMAKAW
CASKchrX41782183GLIPR1L1chr12757374738628VRGCVRAVRGDRKIWDKGLAKMAKAW

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Potential FusionNeoAntigen Information of CASK-GLIPR1L1 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
CASK-GLIPR1L1_41782183_75737473.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-A30:08KIWDKGLAK0.99880.671221
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-B14:01DRKIWDKGL0.99160.56551019
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-B14:02DRKIWDKGL0.99160.56551019
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-B58:02AVRGDRKIW0.91240.8232615
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-B57:01RAVRGDRKIW0.99760.8882515
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-B58:02RAVRGDRKIW0.99020.7411515
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-A02:04KIWDKGLAKM0.9880.57281222
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-B58:01RAVRGDRKIW0.97550.7962515
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-B57:03RAVRGDRKIW0.95490.798515
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-A30:08RKIWDKGLAK0.90310.75851121
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-A30:01KIWDKGLAK0.99880.80841221
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-B57:04AVRGDRKIW0.96370.7069615
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-B58:06AVRGDRKIW0.95620.693615
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-B15:24AVRGDRKIW0.73930.7956615
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-B57:10RAVRGDRKIW0.99760.8882515
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-B57:04RAVRGDRKIW0.99370.7122515
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-B58:06RAVRGDRKIW0.99020.6869515
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-A30:01RKIWDKGLAK0.90210.8791121
CASK-GLIPR1L1chrX41782183chr1275737473105HLA-B57:02RAVRGDRKIW0.86290.7473515

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Potential FusionNeoAntigen Information of CASK-GLIPR1L1 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
CASK-GLIPR1L1_41782183_75737473.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-0840CVRAVRGDRKIWDKG318
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1303CVRAVRGDRKIWDKG318
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1303VRAVRGDRKIWDKGL419
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-13101CVRAVRGDRKIWDKG318
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-13101VRAVRGDRKIWDKGL419
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1310CVRAVRGDRKIWDKG318
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1310VRAVRGDRKIWDKGL419
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1333CVRAVRGDRKIWDKG318
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1333VRAVRGDRKIWDKGL419
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1333GCVRAVRGDRKIWDK217
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1381CVRAVRGDRKIWDKG318
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1381VRAVRGDRKIWDKGL419
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1381GCVRAVRGDRKIWDK217
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1388CVRAVRGDRKIWDKG318
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1388VRAVRGDRKIWDKGL419
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1389CVRAVRGDRKIWDKG318
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1389VRAVRGDRKIWDKGL419
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1390CVRAVRGDRKIWDKG318
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1390VRAVRGDRKIWDKGL419
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1394CVRAVRGDRKIWDKG318
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1394VRAVRGDRKIWDKGL419
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1394GCVRAVRGDRKIWDK217
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1395CVRAVRGDRKIWDKG318
CASK-GLIPR1L1chrX41782183chr1275737473105DRB1-1395VRAVRGDRKIWDKGL419

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Fusion breakpoint peptide structures of CASK-GLIPR1L1

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
706AVRGDRKIWDKGLACASKGLIPR1L1chrX41782183chr1275737473105

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CASK-GLIPR1L1

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN706AVRGDRKIWDKGLA-7.15543-7.26883
HLA-B14:023BVN706AVRGDRKIWDKGLA-4.77435-5.80965
HLA-B52:013W39706AVRGDRKIWDKGLA-6.80875-6.92215
HLA-B52:013W39706AVRGDRKIWDKGLA-4.20386-5.23916
HLA-A11:014UQ2706AVRGDRKIWDKGLA-7.5194-8.5547
HLA-A11:014UQ2706AVRGDRKIWDKGLA-6.9601-7.0735
HLA-A24:025HGA706AVRGDRKIWDKGLA-7.52403-7.63743
HLA-A24:025HGA706AVRGDRKIWDKGLA-5.82433-6.85963
HLA-B27:056PYJ706AVRGDRKIWDKGLA-3.28285-4.31815
HLA-B44:053DX8706AVRGDRKIWDKGLA-5.91172-6.94702
HLA-B44:053DX8706AVRGDRKIWDKGLA-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of CASK-GLIPR1L1

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
CASK-GLIPR1L1chrX41782183chr12757374731019DRKIWDKGLGATCGGAAAATTTGGGATAAAGGTTTA
CASK-GLIPR1L1chrX41782183chr12757374731121RKIWDKGLAKCGGAAAATTTGGGATAAAGGTTTAGCAAAG
CASK-GLIPR1L1chrX41782183chr12757374731221KIWDKGLAKAAAATTTGGGATAAAGGTTTAGCAAAG
CASK-GLIPR1L1chrX41782183chr12757374731222KIWDKGLAKMAAAATTTGGGATAAAGGTTTAGCAAAGATG
CASK-GLIPR1L1chrX41782183chr1275737473515RAVRGDRKIWCGAGCTGTGCGAGGTGATCGGAAAATTTGG
CASK-GLIPR1L1chrX41782183chr1275737473615AVRGDRKIWGCTGTGCGAGGTGATCGGAAAATTTGG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
CASK-GLIPR1L1chrX41782183chr1275737473217GCVRAVRGDRKIWDKGGATGTGTACGAGCTGTGCGAGGTGATCGGAAAATTTGGGATAAA
CASK-GLIPR1L1chrX41782183chr1275737473318CVRAVRGDRKIWDKGTGTGTACGAGCTGTGCGAGGTGATCGGAAAATTTGGGATAAAGGT
CASK-GLIPR1L1chrX41782183chr1275737473419VRAVRGDRKIWDKGLGTACGAGCTGTGCGAGGTGATCGGAAAATTTGGGATAAAGGTTTA

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Information of the samples that have these potential fusion neoantigens of CASK-GLIPR1L1

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
BRCACASK-GLIPR1L1chrX41782183ENST00000318588chr1275737473ENST00000312442TCGA-E2-A14T-01A

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Potential target of CAR-T therapy development for CASK-GLIPR1L1

check button Predicted 3D structure. We used RoseTTAFold.

check buttonRetention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to CASK-GLIPR1L1

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to CASK-GLIPR1L1

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource